Fibronectin extra domain A (EDA) sustains CD133(+)/CD44(+) subpopulation of colorectal cancer cells.
Fibronectin extra domain A (EDA) sustains CD133(+)/CD44(+) subpopulation of colorectal cancer cells.
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DOI：
10.1016/j.scr.2013.05.009
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发表时间：
2013-09
影响因子：
1.2
通讯作者：
Liang, Houjie
中科院分区：
文献类型：
--
作者：
Ou, Juanjuan;Deng, Jia;Wei, Xing;Xie, Ganfeng;Zhou, Rongbin;Yu, Liqing;Liang, Houjie
纤维连接蛋白是一种主要的细胞外基质糖蛋白，具有几种可选择性剪接的变体，包括额外结构域a (EDA)，已被证明通过刺激血管生成和淋巴管生成来促进肿瘤发生。鉴于CD133+/CD44+癌细胞在结直肠癌（CRC）的肿瘤发生中起着至关重要的作用，我们假设纤连蛋白EDA可能通过维持CD133+/CD44+结肠癌细胞的特性来促进肿瘤发生。我们发现晚期结直肠癌患者的肿瘤组织和血清EDA水平明显高于早期结直肠癌患者。此外，我们发现肿瘤组织EDA水平与分化状态和化疗耐药呈正相关，并与结直肠癌患者预后不良相关。我们还发现，在结肠癌细胞SW480中，CD133+/CD44+与CD133−/CD44−细胞表达显著升高的EDA受体整合素α9β1。在SW480细胞中沉默EDA可减少球形细胞的形成和CD133或CD44阳性细胞，这与胚胎干细胞标记物表达减少和分化标记物表达增加有关。阻断整合素α9β1功能可明显逆转EDA过表达的影响。我们也提供了证据表明EDA通过激活整合素/FAK/ERK通路来维持Wnt/β-catenin信号活性。在异种移植模型中，eda沉默的SW480细胞表现出较低的致瘤性和转移能力。综上所述，EDA对于维持CD133+/CD44+结肠癌细胞的特性至关重要。
Fibronectin is a major extracellular matrix glycoprotein with several alternatively spliced variants, including extra domain A (EDA), which was demonstrated to promote tumorigenesis via stimulating angiogenesis and lymphangiogenesis. Given that CD133+/CD44+ cancer cells are critical in tumorigenesis of colorectal cancer (CRC), we hypothesize that fibronectin EDA may promote tumorigenesis by sustaining the properties of CD133+/CD44+ colon cancer cells. We found that tumor tissue and serum EDA levels are substantially higher in advanced versus early stage human CRC. Additionally we showed that tumor tissue EDA levels are positively correlated with differentiation status and chemoresistance, and correlated with a poor prognosis of CRC patients. We also showed that in colon cancer cells SW480, CD133+/CD44+ versus CD133−/CD44− cells express significantly elevated EDA receptor integrin α9β1. Silencing EDA in SW480 cells reduces spheroid formation and cells positive for CD133 or CD44, which is associated with reduced expressions of embryonic stem cell markers and increased expressions of differentiation markers. Blocking integrin α9β1 function strongly reversed the effect of EDA overexpression. We also provided evidence suggesting that EDA sustains Wnt/β-catenin signaling activity via activating integrin/FAK/ERK pathway. In xenograft models, EDA-silenced SW480 cells exhibit reduced tumorigenic and metastatic capacity. In conclusions, EDA is essential for the maintenance of the properties of CD133+/CD44+ colon cancer cells.
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影响因子：
6.4
作者：
Chen, Yuying;Wang, Zhanxiang;Liang, Houjie
通讯作者：
Liang, Houjie
影响因子：
254.7
作者：
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影响因子：
5.2
作者：
Hall, Peter E.;Lathia, Justin D.;Ffrench-Constant, Charles
通讯作者：
Ffrench-Constant, Charles
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
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通讯作者：
Clarke, Michael F.
影响因子：
15.9
作者：
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通讯作者：
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